Structure of the connexin-43 gap junction channel in a putative closed state.
biochemistry
chemical biology
connexin-43
cryo-EM
gap junction channel
hemichannel
human
membrane protein
molecular biophysics
structural biology
structure
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
03 08 2023
03 08 2023
Historique:
medline:
4
8
2023
pubmed:
3
8
2023
entrez:
3
8
2023
Statut:
epublish
Résumé
Gap junction channels (GJCs) mediate intercellular communication by connecting two neighbouring cells and enabling direct exchange of ions and small molecules. Cell coupling via connexin-43 (Cx43) GJCs is important in a wide range of cellular processes in health and disease (Churko and Laird, 2013; Liang et al., 2020; Poelzing and Rosenbaum, 2004), yet the structural basis of Cx43 function and regulation has not been determined until now. Here, we describe the structure of a human Cx43 GJC solved by cryo-EM and single particle analysis at 2.26 Å resolution. The pore region of Cx43 GJC features several lipid-like densities per Cx43 monomer, located close to a putative lateral access site at the monomer boundary. We found a previously undescribed conformation on the cytosolic side of the pore, formed by the N-terminal domain and the transmembrane helix 2 of Cx43 and stabilized by a small molecule. Structures of the Cx43 GJC and hemichannels (HCs) in nanodiscs reveal a similar gate arrangement. The features of the Cx43 GJC and HC cryo-EM maps and the channel properties revealed by molecular dynamics simulations suggest that the captured states of Cx43 are consistent with a closed state.
Identifiants
pubmed: 37535063
doi: 10.7554/eLife.87616
pii: 87616
pmc: PMC10400079
doi:
pii:
Substances chimiques
Connexin 43
0
Ion Channels
0
GJA1 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Swiss National Science Foundation
ID : 184951
Pays : Switzerland
Informations de copyright
© 2023, Qi, Acosta Gutierrez et al.
Déclaration de conflit d'intérêts
CQ, SA, PL, AO, DL, EB, DS, PP, NZ, MB, FG, VK No competing interests declared
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